Functional analysis of granulocyte and monocyte subpopulations in neonates

Ferry Niepel,Anja Lange,Ines Hegge,Matthias Heckmann,Johanna Ruhnau,Antje Vogelgesang

doi:10.1186/s40348-019-0092-y

Ferry Niepel, Anja Lange + Show 4 more

Open Access

https://doi.org/10.1186/s40348-019-0092-y

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Abstract

BackgroundNeonate immune cell functions lack full protection against pathogens. This could be either defect or protective mechanism against overshooting proinflammatory immune responses.We here analysed the function of classical, pro- and anti-inflammatory monocytes and granulocytes from neonates in comparison with adults to investigate if suppressed functions of subpopulations are causative for the unique neonatal immune status. Therefore, reactive oxygen species (ROS) and surface activation markers were quantified in subpopulations.MethodsIn a prospective, longitudinal study granulocyte and monocyte subpopulations were analysed in healthy term infants (> 37 week; n = 13) in comparison with healthy young adults (n = 11). Percentage (%) of cells expressing surface marker (HLA-DR, CD11b, CD62L, CD32, Toll-Like-Receptor-2) and expression per cell, determined by mean fluorescence intensity (MFI), were measured by flow cytometry. ROS production was induced by fMLP, PMA and E. coli in term neonates (> 37 week; n = 13).ResultsClassical granulocytes were down- and proinflammatory granulocytes upregulated in neonates compared with adults. Percentage of TLR-2 expressing granulocytes was increased in neonates. Granulocytic ROS production depended on stimulation. The percentage of anti-inflammatory monocytes was increased, while classical monocytes were reduced in neonates. HLA-DR (%, MFI) showed reduction for all monocyte subpopulations, while CD32, CD11b, CD62L and TLR-2 were differently regulated in comparison with adults.ConclusionsDifferentially regulated granulocyte and monocyte subpopulations indicate a unique state of neonatal immunity to fight infections and prevent dysregulation. Further studies are needed to investigate the role of reduced granulocytic ROS formation and reduced monocytic HLA-DR in active disease.

Highlights

Neonate immune cell functions lack full protection against pathogens
Regulated granulocyte subpopulations Compared with adult controls neonates showed a reduced percentage of classical granulocytes CD16+CD62L+cells while proinflammatory CD16dimCD62L+cells were increased
Activation marker of granulocyte and their subpopulations To analyse the activation profile of granulocytes and their subpopulations in comparison with controls, we analysed the percentage of CD11b, CD32 and Tolllike receptor (TLR)-2 expressing cells as well as the amount of activation marker per cell by mean fluorescence intensity (MFI)

Summary

Introduction

Neonate immune cell functions lack full protection against pathogens This could be either defect or protective mechanism against overshooting proinflammatory immune responses. We here analysed the function of classical, pro- and anti-inflammatory monocytes and granulocytes from neonates in comparison with adults to investigate if suppressed functions of subpopulations are causative for the unique neonatal immune status. Monocytes express less HLA-DR which is known to be a Recently Brook et al stated that the partly lowered antibacterial function of innate immune cells like neutrophils and monocytes is rather a mechanism of protection from overshooting proinflammatory immune responses than a pathologic defect [6]. A broad range of pro-inflammatory plasma proteins is upregulated in septic neonates in comparison with healthy controls, indicating an overwhelming and consuming proinflammatory immune response against infection in early life [7].

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